We seek support to analyze existing data from the Oregon Adolescent Depression Project (OADP) to better understand the long-term course and outcome of major depressive disorder (MOD). The OADP is a multi-generational project that includes a study of prevalence and risk factors for adolescent psychopathology in a large community sample; a longitudinal follow-up of probands' diagnostic course and psychosocial outcomes through young adulthood; a family study of their 1st-degree relatives; and a longitudinal study of their children. We seek to extend prior work with this data set by addressing three broad issues that integrate these components using state of the art data analytic techniques. 1. Psychosocial Functioning and Depressive Symptoms: Growth. Predictors, and Outcomes. Little is known about distinct courses and outcomes of depressive symptoms and psychosocial functioning. We will identify distinct growth trajectories in and reciprocal relations between these areas through young adulthood, and examine prospective predictors and long-term outcomes of distinct trajectories. Identification of unique growth patterns, their risk factors, and their outcomes will have important screening, prevention, and treatment implications for reducing the long-term burden of depression. 2. MOD: Comorbidity. Growth, and Long-term Outcomes. MOD often co-occurs with other psychiatric disorders, particularly substance use disorders (SUDs) and anxiety disorders (ANX). Although MOD comorbidity is associated with elevated impairment in numerous domains, little is known about its etiology and long-term impact. We will examine MDD-SUD and MDD-ANX comorbidity models based upon patterns of risk and protective factors and long-term outcomes of pure and comorbid disorders. Identification of prospective predictors and long-term outcomes of comorbidity will improve nosology and inform screening and prevention strategies. 3. Intergenerational Outcomes: Transmission of Psvchopathology across Three Generations. Evidence indicates that MOD is familial, yet the circumstances under which and mechanisms by which MOD is transmitted across generations remain unknown. We will examine moderational and mediational models of transmission between grandparents, parents, and children, and examine the diagnostic specificity of intergenerational transmission of psychopathology. We will also examine risk and protective factor profiles according to familial MDD patterns. Uncovering the conditions, mechanisms of, and risk and protective factors for MDD transmission across generations will have important implications for identifying those at risk for the disorder and point to potential targets for intervention. [unreadable] [unreadable] [unreadable] [unreadable]